Risk Factors for Developing T790M Mutation in Patients with EGFR-Mutated Advanced Non-Small Cell Lung Cancer

Abstract

Previous studies suggested that third-generation EGFR-TKIs only improved the survival of patients with T790M-positive mutation, not for all EGFR-mutated NSCLC patients. The aim of the current study was to explore the possible risk factors for developing T790M-positive mutation during the course of EGFR-TKIs therapy, and to identify the potential patients most likely to benefit from first-line osimertinib treatment. A total of 222 patients with EGFR-mutated advanced NSCLC were analyzed in our institute between 2012 and 2018 were included. The progression-free survival (PFS), overall survival (OS) were calculated, and the cumulative incidence of T790M-positive mutation was respectively calculated by the Kaplan-Meier method, and multivariate cox regression analysis was used to investigate the independent risk factors for developing T790M-positive mutation. At last, survival analyses was used to demonstrate significant differences between different risk subgroups stratified by risk factors. After a median follow-up time of 22.8 months, a total of 70 patients developed T790M positive mutation. Compared to these patients, patients not-developing T790M positive mutation were at a significantly higher risk on OS (HR=2.171, p=0.003), but no difference on PFS of first-generation EGFR-TKIs treatment (p=0.077). Moreover, the multivariate analysis indicated that BMI≤ 25 (p=0.031), higher NSE level before treatment (p=0.013), and retroperitoneal LN metastasis (p=0.002) were independent high-risk factors of developing T790M positive mutation. At last, the actuarial risk of developing T790M positive mutation at 1 year were 6.6% in patients with 0∼1 risk factor and 31.5% in patients with 2∼3 risk factors. Patients developing T790M positive mutation during the course of EGFR-TKIs treatment had a better OS, whereas similar PFS of first-generation EGFR-TKIs. BMI≤ 25, NSE>17.9 ng/ml, and retroperitoneal LN metastasis were independent risk factors for developing T790M positive mutation. The possibilities of selectively using osimertinib as first-line treatment in higher-risk patients should be further explored in the future.